alexa miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Metabolomics:Open Access

Author(s): Acunzo M, Visone R, Romano G, Veronese A, Lovat F,

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Abstract Non-small cell lung cancer (NSCLC) accounts for ∼80\% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.
This article was published in Oncogene and referenced in Metabolomics:Open Access

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